The determinants of myocardial abnormalities in alcoholics are presumably varied. Preclinical cardiomyopathy as a recognized entity has been observed in several laboratories an can serve as a useful model for the study of pathogenesis since secondary factors related to heart failure per se, do not complicate the issue. Our previous observation that female subjects with hepatic cirrhosis and apparently similar alcoholic history as male cirrhotics did not exhibit the preclinical abnormality observed in males, serves as a focal point for consideration of pathogenesis. To utilize a more controlled preparation, the effects of chronic alcoholism will be assessed in male and female mongrel dogs in terms of neurohumoral responses, as potential determinants of the alterations in myocardial function and electrical stability, as well as cardiac composition. The information derived from these studies will serve as a basis for investigations in selected human alcoholics. Secondly, since most alcoholic subjects who develop cardiac abnormalities are cigarette smokers, we propose to evaluate the chronic influence of ethanol and the major cardioactive component of tobacco, nicotine. We have previously observed that animals chronically smoking cigarettes accumulated collagen in the interstitium of the left ventricle associated with diminished contractility. These responses were duplicated in the animals exposed to nicotine injections on a chronic basis. In view of the fact that long-term tracheostomy preparations in the large mongrel dog are not feasible and since chronic nicotine administration qualitatively simulated many of the responses to chronic smoking, we propose to study the effects of the alkaloid administered chronically, with and without ethanol. The role of catecholamines will be of particular interest.